Decrease in cytosolic phospholipase A2α mRNA levels by reactive oxygen species via MAP kinase pathways in PC12 cells:: effects of dopaminergic neurotoxins

Excess production of reactive oxygen species (ROS), including H2O2, leads to neuronal death in pathological conditions. Although ROS stimulates a-type cytosolic phospholipase A(2) (cPLA(2)alpha) activity, their role in cPLA2a expression has not been elucidated. We investigated the effect of ROS on cPLA(2)alpha mRNA levels and signaling pathways in rat pheochromocytoma. PC 12 cells. Treatment with H2O2 and xanthine-xanthine oxidase (X/XO) for 4 h decreased cPLA(2)alpha mRNA levels without changing the mRNA levels of other tested proteins. H2O2 and X/XO caused cell toxicity not after 4 h but 24 h after their addition. The H2O2-induced decrease in cPLA(2)alpha mRNA levels was inhibited in cells treated with N-acetyl-cysteine and selective inhibitors of mitogen-activated protein kinase (MAPK) pathways (extracellular signal-regulated kinase and p38 MAPK). Treatment with dopaminergic neurotoxins, including 1,2,3,4-tetrabydroisoquinoline (TIQ)-inducing ROS formation, decreased cPLA(2)alpha mRNA levels. These findings suggest that ROS decreases cPLA(2)alpha mRNA levels via MAPK pathways in PC12 cells. (C) 2004 Elsevier Inc. All rights reserved.